Staphylococcus aureus is arguably the most problematic pathogen faced by modern healthcare systems today, owing in large part to the persistent emergence of antibiotic resistant strains. This is perhaps most evident in the recent appearance of methicillin-resistant strains even among isolates causing community-acquired infection. Moreover, many of these strains, most notably those of the USA300 clonal lineage, have the capacity to cause serious, life-threatening infection even in otherwise healthy individuals. This accounts in large part for the observation that, in the United States alone in 2005, an estimated 94,360 patients suffered from invasive infection caused by methicillin-resistant S. aureus (MRSA), with approximately 18,650 resulting in a fatal outcome.
The continued emergence of antibiotic-resistant strains has created an urgent need for new antimicrobial agents. However, many S. aureus infections are recalcitrant to antimicrobials even in the absence of issues related to acquired resistance. A primary contributing factor to this recalcitrance is formation of a biofilm on both native tissues and indwelling medical devices. This is due to the fact that the biofilm confers a degree of intrinsic resistance that often necessitates surgical intervention to debride infected tissues and/or remove infected devices. For example, one study found that nearly half of patients with implanted orthopedic devices admitted to a hospital with S. aureus bacteremia had developed an implant-associated infection. Thus, while there is an urgent need for new antibiotics, there is an equally urgent need to develop therapeutic agents that could be used to limit biofilm formation. While such agents would not necessarily function as antibiotics in and of themselves, they could be used as a prophylactic to limit biofilm formation (e.g. coating for implanted devices, surgical lavage, or pre-operative oral prophylaxis) or as a therapeutic to be used in conjunction with more conventional antibiotics to treat an established biofilm-associated infection.